mAbs最新文献

{"title":"A novel <i>in vitro</i> serum stability assay for antibody therapeutics incorporating internal standards.","authors":"Yihan Li, Rosendo Villafuerte-Vega, Vikram M Shenoy, Heidi M Jackson, Yuting Wang, Karen E Parrish, Gary J Jenkins, Hetal Sarvaiya","doi":"10.1080/19420862.2025.2479529","DOIUrl":"10.1080/19420862.2025.2479529","url":null,"abstract":"<p><p>Antibody-based therapeutics have demonstrated remarkable therapeutic benefit, but their susceptibility to biotransformation and degradation in the body can affect their safety, efficacy, and pharmacokinetic/pharmacodynamic (PK/PD) profiles. <i>In vitro</i> stability assessments play a pivotal role in proactively identifying potential liabilities of antibody therapeutics prior to animal studies. Liquid chromatography-mass spectrometry (LC-MS)-based <i>in vitro</i> stability assays has been developed and adopted in the biopharmaceutical industry for the characterization of antibody-based therapeutics. However, these methodologies often overlook operational error and random variation during sample preparation and analysis, leading to inaccurate stability estimation. To address this limitation, we have developed an LC-MS-based <i>in vitro</i> serum stability assessment that incorporates two internal standards (ISs), National Institute of Standards and Technology monoclonal antibody (NISTmAb) and its crystallizable fragment (Fc), to improve assay performance. Our method involves three steps: incubation of antibody therapeutics along with an IS in biological matrices, affinity purification, and LC-MS analysis. The stability of 21 monoclonal or bispecific antibodies was assessed in serums of preclinical species using this method. Our results showed improved accuracy and precision of recovery calculations with the incorporation of ISs, enabling a more confident stability assessment even in the absence of biotransformation or aggregation. <i>In vitro</i> stability correlated with <i>in vivo</i> exposure, suggesting that this <i>in vitro</i> assay could serve as a routine screening tool to select and advance stable antibody therapeutic candidates for subsequent <i>in vivo</i> studies.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2479529"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted fusion of antibody-secreting cells: Unlocking monoclonal antibody production with hybridoma technology.","authors":"Fanny Rousseau, Catherine Menier, Patricia Brochard, Stéphanie Simon, Karla Perez-Toralla, Anne Wijkhuisen","doi":"10.1080/19420862.2025.2510336","DOIUrl":"10.1080/19420862.2025.2510336","url":null,"abstract":"<p><p>Hybridomas, the first method for creating monoclonal antibodies (mAbs), were reported 50 years ago. This approach, which transformed biomedical research and laid the foundation for many of the current therapeutic, diagnostic, and research reagent applications of mAbs, is still used today, despite reported low fusion yields between short-lived B cells and immortal myeloma cells. To improve hybridoma production yields and accelerate development of new mAbs, we addressed two key limitations: 1) random pairing between myeloma cells and antibody-producing cells, and 2) low efficiency of the polyethylene-glycol-mediated fusion process. We first characterized and isolated antibody-secreting cells (ASCs) from the spleen of immunized mice before cell fusion to increase the probability of successive pairing between the most suitable cell fusion partners and favor the generation of functional hybridomas. Specifically, we developed an optimized workflow combining fluorescence-activated cell sorting with antibody secretion assays, using a panel of five cell-surface markers (CD3, TACI, CD138, MHC-II, and B220) to identify a distinct ASC subset with key characteristics. Such ASCs exhibited a plasmablast phenotype with high MHC-II expression and secreted high levels of antigen (Ag)-specific antibodies in immunized mice. We then implemented a cell electrofusion procedure adapted to low cell numbers (<10⁶ cells), in order to perform the targeted electrofusion of TACI^highCD138^high sorted ASCs. This targeted approach yielded viable hybridomas in 100% of seeded culture wells compared to only 40% for the electrofusion of unsorted cells. In particular, over 60% of hybridomas generated from TACI^highCD138^high sorted ASCs secreted Ag-specific mAbs, including IgGs with high Ag binding affinity (<10^-9 M). These results pave the way for a high-yield mAb production method via cell fusion, with the potential to streamline hybridoma generation and thereby expand access to mAbs.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2510336"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational design of therapeutic antibodies with improved developability: efficient traversal of binder landscapes and rescue of escape mutations.","authors":"Frédéric A Dreyer, Constantin Schneider, Aleksandr Kovaltsuk, Daniel Cutting, Matthew J Byrne, Daniel A Nissley, Henry Kenlay, Claire Marks, David Errington, Richard J Gildea, David Damerell, Pedro Tizei, Wilawan Bunjobpol, John F Darby, Ieva Drulyte, Daniel L Hurdiss, Sachin Surade, Newton Wahome, Douglas E V Pires, Charlotte M Deane","doi":"10.1080/19420862.2025.2511220","DOIUrl":"https://doi.org/10.1080/19420862.2025.2511220","url":null,"abstract":"<p><p>Developing therapeutic antibodies is a challenging endeavor, often requiring large-scale screening to produce initial binders, that still often require optimization for developability. We present a computational pipeline for the discovery and design of therapeutic antibody candidates, which incorporates physics- and AI-based methods for the generation, assessment, and validation of candidate antibodies with improved developability against diverse epitopes, via efficient few-shot experimental screens. We demonstrate that these orthogonal methods can lead to promising designs. We evaluated our approach by experimentally testing a small number of candidates against multiple SARS-CoV-2 variants in three different tasks: (i) traversing sequence landscapes of binders, we identify highly sequence dissimilar antibodies that retain binding to the Wuhan strain, (ii) rescuing binding from escape mutations, we show up to 54% of designs gain binding affinity to a new subvariant and (iii) improving developability characteristics of antibodies while retaining binding properties. These results together demonstrate an end-to-end antibody design pipeline with applicability across a wide range of antibody design tasks. We experimentally characterized binding against different antigen targets, developability profiles, and cryo-EM structures of designed antibodies. Our work demonstrates how combined AI and physics computational methods improve productivity and viability of antibody designs.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2511220"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Online native hydrophobic interaction chromatography-mass spectrometry of antibody-drug conjugates.","authors":"Trevor Kempen, Lance Cadang, Yuchen Fan, Kelly Zhang, Tao Chen, Bingchuan Wei","doi":"10.1080/19420862.2024.2446304","DOIUrl":"https://doi.org/10.1080/19420862.2024.2446304","url":null,"abstract":"<p><p>Hydrophobic interaction chromatography (HIC) is commonly used to determine the drug-to-antibody ratio (DAR) and drug load distribution of antibody-drug conjugates (ADCs). However, identifying various DAR species separated by HIC is challenging due to the traditional use of mobile phases that are incompatible with mass spectrometry (MS). Existing approaches used to couple HIC with MS often encounter issues, such as complex instrumentation, compromised separation efficiency, and reduced MS sensitivity. In this study, we introduce a 22-min online native HIC-MS method for the separation and characterization of different DAR species in ADCs, addressing these challenges. The key novelty of this method is the use of ammonium tartrate, a kosmotropic and thermally decomposable salt, as the salt of HIC mobile phase, ensuring both excellent HIC separation and MS compatibility. Additionally, an ultrashort size exclusion chromatography step is integrated for online sample cleaning, enhancing MS sensitivity. This platform native HIC-MS method offers a rapid, sensitive, and robust solution for comprehensive profiling of DAR species in ADCs with a simple and cost-effective instrumental setup.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2446304"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost and supply considerations for antibody therapeutics.","authors":"Chun Chen, Zoe Garcia, David Chen, Hong Liu, Piper Trelstad","doi":"10.1080/19420862.2025.2451789","DOIUrl":"10.1080/19420862.2025.2451789","url":null,"abstract":"<p><p>Monoclonal antibodies (mAbs) and mAb-derived biologics have achieved substantial success across various therapeutic areas over recent decades. Their widespread adoption, however, remains constrained due to high prices and challenges in supply. Here, we examine the general price and cost structure of mAbs and mAb-derived therapeutics and identify directions to improve affordability and strategies to ensure supply. Mainstream and emerging biomanufacturing formats and their implications on cost and supply are discussed. We also summarize modeling tools used across industry for process economics analysis, emphasizing the importance of this assessment throughout the product development lifecycle. A comprehensive understanding of cost and supply scenarios will empower industry players to thrive despite competition, navigate supply challenges, and broaden access to mAb therapeutics for more patients.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2451789"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of long-term stability of high-concentration formulations to support rapid development of antibodies against SARS-CoV-2.","authors":"Lin Luo, Michael Meleties, Julie Beaudet, Yuan Cao, Wenhua Wang, Qingyan Hu, Sarah Sidnam, Michele Lastro, Dingjiang Liu, Mohammed Shameem","doi":"10.1080/19420862.2025.2471465","DOIUrl":"10.1080/19420862.2025.2471465","url":null,"abstract":"<p><p>Long-term stability of antibody therapeutics is required to ensure their safety and efficacy when administered to patients. However, obtaining shelf life supporting, long-term stability data are often a limiting factor for new drug candidates starting clinical trials. Predictive stability, which uses short-term accelerated stability data and kinetic modeling to forecast long-term storage stability, has the potential to provide justification to support establishing shelf life, although its application for biologics has only recently gained traction. We have developed empirical models for key stability-indicating quality attributes of high-concentration IgG1 liquid formulations. Using short-term accelerated stability data and Arrhenius-based approaches, including Arrhenius plotting and global fitting, we applied empirical kinetics to predict the long-term stability of seven anti-SARS-CoV-2 antibodies. Arrhenius plotting determines kinetics by plotting the reaction rate logarithm against inverse temperature, while global fitting simultaneously fits a model with data at multiple temperatures to comprehensively understand kinetics. These approaches were used to fit empirical kinetics to short-term data to predict long-term stability, leveraging stability data collected at shelf life storage conditions (5°C) and at least 1 month of accelerated stability data at three temperatures within 25-40°C. Model accuracy was demonstrated using long-term (up to 36 months) storage stability data at 5°C. The approach was applied successfully in anti-SARS-CoV-2 antibody drug development to enable rapid regulatory Investigational New Drug and Investigational Medicinal Product Dossier filings and support shelf life justification where limited shelf life stability data were available at the time of filing. Our results show that successful long-term stability predictions and shelf life estimation can be achieved with high accuracy using 1 month of accelerated stability data, which may be especially beneficial for rapid response programs with severely constrained development timelines. Thus, the described model demonstrates how predictive stability models can, in addition to enabling earlier decision-making in drug development, also be used to justify product shelf life in regulatory submissions, enabling faster patient access to life-saving drug products.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2471465"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid affinity-based purification of multi-specific antibodies using Kappa Select and Protein L.","authors":"Kalie Mix, Tingwan Sun, Brian Hall, Jocelyn Newton, Christina Eng, Yongjing Guo, David Reczek","doi":"10.1080/19420862.2025.2483272","DOIUrl":"10.1080/19420862.2025.2483272","url":null,"abstract":"<p><p>Multispecific antibodies (msAbs) are becoming more prevalent as formats of choice for therapeutic antibody development due to their ability to modulate multiple biological targets. However, msAbs present unique protein production challenges due to product-related impurities, which are difficult to remove without loss of the protein of interest. Here, we report a versatile approach to remove product-related impurities by altering the binding affinity of light chains to Kappa Select (KS) or Protein L (Pro-L) resins. Introduction of amino acid mutations in the constant light chain domain or Framework 1 of the light chain abolished binding to KS and Pro-L resins, respectively, while antigen binding affinity remained intact. These purification-enabling mutations (PEMs) did not affect the thermal stability or purity of the proteins tested. In conjunction with PEMs, we demonstrate the design and application of an entirely affinity-based purification scheme employing Protein A (Pro-A), followed by KS and Pro-L affinity resins, to remove light chain mispaired species in Y-shaped bispecific antibodies and crossover dual variable domain (CODV) tri-specific antibodies. In principle, this purification scheme could be applied to any IgG-like msAb since it is compatible with Fc knobs-into-holes mutations and Fab arm charge-pair mutations. Moreover, it should be adaptable across a range of production scales and medium to high-throughput purification workflows within early-stage research.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2483272"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design of orthogonal constant domain interfaces to aid proper heavy/light chain pairing of bispecific antibodies.","authors":"Kyle A Barlow, Michael B Battles, Michael E Brown, Kaleigh Canfield, Xiaojun Lu, Heather Lynaugh, Morgan Morrill, C Garrett Rappazzo, Saira P Reyes, Chanita Sandberg, Beth Sharkey, Christin Strong, Jingfu Zhao, Arvind Sivasubramanian","doi":"10.1080/19420862.2025.2479531","DOIUrl":"10.1080/19420862.2025.2479531","url":null,"abstract":"<p><p>The correct pairing of cognate heavy and light chains is critical to the efficient manufacturing of IgG-like bispecific antibodies (bsAbs) from a single host cell. We present a general solution for the elimination of heavy chain (HC):light chain (LC) mispairs in bsAbs with <math><mi>κ</mi></math> LCs via the use of two orthogonal constant domain (C_H1:C<math><mi>κ</mi></math>) interfaces comprising computationally designed amino acid substitutions. Substitutions were designed by Rosetta to introduce novel hydrogen bond (H-bond) networks at the C_H1:C<math><mi>κ</mi></math> interface, followed by Rosetta energy calculations to identify designs with enhanced pairing specificity and interface stability. Our final design, featuring a total of 11 amino acid substitutions across two Fab constant regions, was tested on a set of six IgG-like bsAbs featuring a diverse set of unmodified human antibody variable domains. Purity assessments showed near-complete elimination of LC mispairs, including in cases with high baseline mispairing with wild-type constant domains. The engineered bsAbs broadly recapitulated the antigen-binding and biophysical developability properties of their monospecific counterparts and no adverse immunogenicity signal was identified by an in vitro assay. Fab crystal structures containing engineered constant domain interfaces revealed no major perturbations relative to the wild-type coordinates and validated the presence of the designed hydrogen bond interactions. Our work enables the facile assembly of independently discovered IgG-like bispecific antibodies in a single-cell host and demonstrates a streamlined and generalizable computational and experimental workflow for redesigning conserved protein:protein interfaces.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2479531"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of how antigen mutations disrupt antibody binding interactions toward enabling rapid and reliable antibody repurposing.","authors":"Sumaiya Islam, Varun M Chauhan, Robert J Pantazes","doi":"10.1080/19420862.2024.2440586","DOIUrl":"10.1080/19420862.2024.2440586","url":null,"abstract":"<p><p>Antibody repurposing is the process of changing a known antibody so that it binds to a mutated antigen. One of the findings to emerge from the Coronavirus Disease 2019 (COVID-19) pandemic was that it was possible to repurpose neutralizing antibodies for Severe Acute Respiratory Syndrome, a related disease, to work for COVID-19. Thus, antibody repurposing is a possible pathway to prepare for and respond to future pandemics, as well as personalizing cancer therapies. For antibodies to be successfully repurposed, it is necessary to know both how antigen mutations disrupt their binding and how they should be mutated to recover binding, with this work describing an analysis to address the first of these topics. Every possible antigen point mutation in the interface of 246 antibody-protein complexes were analyzed using the Rosetta molecular mechanics force field. The results highlight a number of features of how antigen mutations affect antibody binding, including the effects of mutating critical hotspot residues versus other positions, how many mutations are necessary to be likely to disrupt binding, the prevalence of indirect effects of mutations on binding, and the relative importance of changing attractive versus repulsive energies. These data are expected to be useful in guiding future antibody repurposing experiments.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2440586"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of human pharmacokinetics of Fc-engineered therapeutic monoclonal antibodies using human FcRn transgenic mice.","authors":"Kenta Haraya, Takuya Ichikawa, Naoaki Murao, Hitoshi Katada, Taichi Kuramochi","doi":"10.1080/19420862.2025.2484443","DOIUrl":"10.1080/19420862.2025.2484443","url":null,"abstract":"<p><p>Human FcRn transgenic mice (Tg32) have been widely used to evaluate the pharmacokinetics of mAbs and predict human pharmacokinetics. This study aims to establish an approach for predicting the human pharmacokinetics of Fc-engineered mAbs with enhanced FcRn binding mutations using Tg32 mice. MAbs were intravenously administered at 10 mg/kg in the absence or presence of IVIG (1000 mg/kg) in Tg32 mice. Pharmacokinetic parameters (CL, Q, V_c, and V_p) estimated in Tg32 mice were compared with clinical data. Optimal allometric scaling exponents were determined to improve the accuracy of human pharmacokinetic predictions for Fc-engineered mAbs. Moreover, we predicted the plasma concentration-time profile after IV injection in humans using parameters estimated based on an optimized exponent. While normal mAbs exhibited a higher CL in the presence of IVIG compared to its absence, Fc-engineered mAbs showed comparable CL in both conditions. The larger difference in CL between normal and Fc-engineered mAbs observed in the presence of IVIG closely matched clinical study results. A significant positive correlation between Tg32 mice and humans was observed in the CL of Fc-engineered mAbs in both the absence and presence of IVIG. The estimated optimal exponents for CL, Q, V_c, and V_p were 0.73, 0.60, 0.95, and 0.87, respectively. Using these exponents, the plasma mAb concentration-time profile after IV injection in humans was accurately predicted. This study establishes a robust methodology for accurately predicting the human pharmacokinetics of Fc-engineered mAbs using Tg32 mice, achieving prediction accuracy comparable to that of cynomolgus monkeys. This approach, as a viable alternative to cynomolgus monkeys, can accelerate the preclinical development of promising Fc-engineered mAbs with enhanced FcRn binding.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2484443"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}